V-112 | Wnt canonical pathway activity in reward-related brain regions underlying social isolation-induced cocaine sensitization in adolescent rats.

Neurochemistry and Neuropharmacology
Author: Abraham Isaac Ramirez | Email: abrahamrami477@gmail.com

Abraham Ramirez^1°2°, Lucia Trossero^1°,Cintia Konjuh^1°, Alejandra Pacchioni^1°2°

^1° Laboratorio de Toxicología Experimental, Departamento de Ciencias de los Alimentos y el Medio Ambiente, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario,
^2° CONICET-CCT Rosario

Cocaine use disorder is a chronic disease where users transition from occasional to compulsive drug use. It has been shown that stress contributes to this progression. The reward brain circuit, which undergoes continued development during adolescence, is affected by stress and drugs. Our team aims to understand the role of stress from adolescent social isolation (SI) on the vulnerability to cocaine in rats. In addition, we study the role of the Wnt canonical pathway by measuring b-catenin levels in the brain´s reward areas. Previously, we demonstrated that changes in the Wnt canonical pathway are associated with both cocaine sensitization and adolescent SI. Our study sought to evaluate if 5 days of SI (PND30-35) would induce cocaine sensitization on PND45 as well as changes in β-catenin levels in the Prefrontal Cortex (PFC) and Nucleus Accumbens (NAcc), in female and male rats. Our results revealed that SI induced cocaine (5mg/kg i.p.) sensitization only in male rats (p<0,05). Also, isolated males showed lower exploratory response (p<0,05) and higher anxiety levels (p<0,05) than control. In contrast, female rats showed similar cocaine responses regardless of previous SI exposure. At the molecular level, Si-induced cocaine sensitization was linked to decreased b-catenin levels in the PFC (p<0,05) and increased levels in the NAcc (p<0,05). These findings propose the Wnt canonical pathway as a neuroadaptation on the impact of adolescent stress over cocaine effects.